On the physical interpretation of QSAR models

被引:58
作者
Stanton, DT [1 ]
机构
[1] Procter & Gamble, Miami Valley Labs, Corp Res, Div Chem Technol, Cincinnati, OH 45252 USA
来源
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES | 2003年 / 43卷 / 05期
关键词
D O I
10.1021/ci0340658
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Multidimensional quantitative structure-activity models (QSAR) developed using molecular structure descriptors and regression analysis techniques have found wide utility and acceptance. However, it is often difficult to extract a physical interpretation of such models because of the types of descriptors involved and the multidimensional nature of the model. The work described here illustrates a method of model interpretation that employs partial least squares (PLS) analysis. Structure-activity relationship information is derived from the positions of specific sets of structures in the PLS score plots and the weights for each variable in the PLS components. Using these data, information regarding major structure-activity trends, trend exceptions, and unique or outlying observations is easily obtained. Examples of this methodology are illustrated using QSAR equations developed for the inhibition of quinolone-resistant bacterial DNA gyrase and human topoisomerase-II inhibition by a series of quinolone antibacterial agents.
引用
收藏
页码:1423 / 1433
页数:11
相关论文
共 30 条
[1]   PREDICTIVE ABILITY OF REGRESSION-MODELS .2. SELECTION OF THE BEST PREDICTIVE PLS MODEL [J].
BARONI, M ;
CLEMENTI, S ;
CRUCIANI, G ;
COSTANTINO, G ;
RIGANELLI, D ;
OBERRAUCH, E .
JOURNAL OF CHEMOMETRICS, 1992, 6 (06) :347-356
[2]   GENERATING OPTIMAL LINEAR PLS ESTIMATIONS (GOLPE) - AN ADVANCED CHEMOMETRIC TOOL FOR HANDLING 3D-QSAR PROBLEMS [J].
BARONI, M ;
COSTANTINO, G ;
CRUCIANI, G ;
RIGANELLI, D ;
VALIGI, R ;
CLEMENTI, S .
QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS, 1993, 12 (01) :9-20
[3]   GENERATION OF DESCRIPTORS FROM MOLECULAR-STRUCTURES [J].
BRUGGER, WE ;
STUPER, AJ ;
JURS, PC .
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1976, 16 (02) :105-110
[4]   ATOMIC CHARGE CALCULATIONS FOR QUANTITATIVE STRUCTURE PROPERTY RELATIONSHIPS [J].
DIXON, SL ;
JURS, PC .
JOURNAL OF COMPUTATIONAL CHEMISTRY, 1992, 13 (04) :492-504
[5]  
Dunn III W. J., 1989, TETRAHEDRON COMPUT M, V2, P349, DOI DOI 10.1016/0898-5529(89)90004-3
[6]   PARTIAL LEAST-SQUARES REGRESSION - A TUTORIAL [J].
GELADI, P ;
KOWALSKI, BR .
ANALYTICA CHIMICA ACTA, 1986, 185 :1-17
[7]  
IVANCIUC O, 1999, TOPOLOGICAL INDICES, P59
[8]  
JURS PC, COMPUTER ASSISTED DR, P103
[9]  
Kier L.B., 1986, Molecular Connectivity in Structure-Activity Analysis
[10]  
Kier L. H., 1976, Molecular Connectivity in Chemistry and Drug Research